The molecular mechanisms of cytokinesis are poorly understood, despite its being the fundamental event of cell division. The overall goal of the proposed research is to increase our understanding of this process, specifically by identifying proteins that participate in linking the contractile ring to the plasma membrane during cytokinesis. The novel phenotype of Drosophila frodo mutant cells indicates that the frodo gene product promotes or stabilizes this linkage in the establishment of the cleavage furrow. Cloning the frodo gene and determining the encoded protein s primary structure may reveal putative structural motifs that bear on Frodo function. Motifs and homologies identified by conceptual translation of the gene will be mutated to test their requirement for Frodo activity in cytokinesis. Antibodies raised against fragments of recombinant wild-type Frodo will be employed in an immunocytological investigation of the protein's subcellular localization in wild-type and mutant backgrounds. It will be determined whether Frodo colocalizes with known structures relevant to cytokinesis such as the contractile ring or central spindle and whether other proteins are dependent on the presence of Frodo for their localization. These studies should provide insight into Frodo function increase our understanding of cytokinesis. An improved molecular understanding of this aspect of cell division may allow for new therapeutic opportunities in cancer treatment.